Industry is searching for fluorinating agents which are site-selective towards organic, especially carbanionic, substrates, especially for use in preparing pharmacologically active compounds. A number of such electrophilic fluorinating agents are known but, until recently were limited in their commercial utility because such agents were expensive, hazardous, inconvenient to handle, unstable and/or insufficiently selective for general use.
U.S. Pat. No. 5,086,178 discloses N-fluorinated diazabicycloalkane derivatives which are stable, effective electrophilic fluorinating agents represented by the following Formula A: ##STR1## wherein n represents 0, 1 or 2;
R represents a quaternizing organic group; PA1 each R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represents hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.6 alkyl-substituted aryl or aryl-substituted C.sub.1 -C.sub.6 alkyl; and PA1 each X.sup.- independently represents a counterion or 2X.sup.- represents a single divalent counterion. PA1 each R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represents hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.6 alkyl-substituted aryl or aryl-substituted C.sub.1 -C.sub.6 alkyl; and each X.sup.- represents a counterion or 2X.sup.- represents a single divalent counterion. PA1 each R.sup.l, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represents hydrogen, C.sub.1 -C.sub.6 alkyl, aryl, C.sub.1 -C.sub.6 alkyl-substituted aryl or aryl-substituted C.sub.1 -C.sub.6 alkyl; each X.sup.- represents a counterion.; and Y represents a readily fluorinatable Lewis acid.
U.S. Pat. No. 5,086,178 discloses a process for preparing the compounds of Formula I (see Detailed Description of the Invention) wherein the corresponding N-substituted diazabicycloalkane derivative of the following Formula B are fluorinated to reach the enumerated compositions. ##STR2## wherein n, R, R.sup.1 to R.sup.5, and X.sup.- are as defined above.
When fluoride is not required as a counterion in the N-substituted diazabicycloalkane derivative of Formula I, fluorination is conducted in the presence of an alkali metal salt to provide the required counterion or an alkali metal salt is added to the fluorination product in a separate step to replace the fluoride ion. However, this procedure involves forming an alkali metal fluoride by-product and the product is difficult to free from the resulting F.sup.- and adventitious HF.sup.-.sub.2 ions. Further, a substantial quantity of organic solvent, usually acetonitrile, is required in order to avoid co-precipitation of the product.
It was unexpectedly found that these problems could be overcome by addition of a readily fluorinatable Lewis acid prior to, during, or after the fluorination step. The term "readily fluorinatable Lewis acid" means a Lewis acid (Y) which readily combines with F.sup.- to form YF.sup.- and includes adducts of the free Lewis acid, such as those derived from amines or from ethers. This improved process is the subject of copending U.S. patent application Ser. No. 07/973,437 filed 11th Nov. 1992.
When the Lewis acid is added prior to fluorination, a novel azaazoniabicycloalkane-Lewis acid adduct of the following Formula C is formed as an isolatable intermediate: ##STR3## wherein n, R, R.sup.1 to R.sup.5, and n are as defined above and Y is a readily fluorinatable Lewis acid.
1,4-Diazabicyclo[2.2.2]octane (otherwise tetra-ethylenediamine, TEDA) is commercially available under, for example, the Trade Mark DABCO (Air Products and Chemicals Inc.) for use in the manufacture of urethane foams, elastomers and coatings, epoxy resins, and the like articles. N,N-Tetrahalo-1,4-diazabicyclo[2.2.2]-octanes in which the halogen is chlorine, bromine or iodine are known and can readily be prepared from 1,4-diaza-bicyclo[2.2.2]octane by, for example, treatment with the halogen in carbon tetrachloride. However, the corresponding tetrafluoro compound is unknown and cannot be prepared in an analogous manner. Attempts to fluorinate 1,4-diazabicyclo[2.2.2]octane with fluorine to produce 1,4-difluoro-1,4-diazoniabicyclo[2.2.2]octane difluoride gave an unidentified white solid which showed some fluorinating capacity but readily decomposed at ambient temperature into a coloured material having no electrophilic fluorinating power.
J. M. Van Paasschen et al. (Can. J. Chem. 1975, 53, 723-726) discloses, inter alia, the preparation of triethylenediamine trifluoromonoborane by reaction of triethylenediamine with trimethylamine-trifluoroborane.
J. M. Van Paasschen et al. (J. Inorg. Nucl. Chem. 1976, 38, 2322-2323) discloses, inter alia, the preparation of quinuclidine-trifluoromonoborane (1-azabicyclo[2.2.2.]-octane-trifluoromonoborane) by treating quinuclidine with trimethylaminetrifluoroborane.
EP-A-0204535 (published 10th Dec. 1986) discloses, inter alia, the preparation of N-fluoropyridinium salts by reaction of optionally substituted pyridine with fluorine and a Lewis acid. In the exemplified processes, a mixture of fluorine and nitrogen was passed through a solution of pyridine or substituted pyridine in acetonitrile and the Lewis acid subsequently added (Examples 41-44) or through a solution of both substituted pyridine and the Lewis acid (Example 45).
T. Umemoto et al. (Bull. Chem. Soc. Jpn. 1991, 64, 1081-1092) also discloses, inter alia, the preparation of N-fluoropyridinium salts by said processes of EP-A-0204535. They report that fluorination of pyridine-BF.sub.3 complex yielded only trace amounts of N-fluoropyridinium tetra-fluoroborate but that fluorination of 3,5-dichloro- and pentachloro- pyridine-BF.sub.3 complexes provided the corresponding tetrafluoroborate in substantial yields (79% and 87% respectively). It appears that it was necessary to use trifluoroacetic acid as the solvent when preparing N-fluoropentachloropyridinium tetrafluoroborate. Trifluoroacetic acid is not usually used as a solvent and is substantially more expensive and more difficult to remove from the product than acetonitrile.
U.S. Pat. No. 4,935,519 discloses that, contrary to the teachings of EP-A0204535 and of T. Umemoto et al. (supra), the fluorination of pyridine-BF.sub.3 complex by passing a fluorine/nitrogen mixture through a solution thereof in acetonitrile, preferably containing water, yields N-fluoro-pyridinium pyridine heptafluorodiborate. However, it is believed that the product actually is N-fluoropyridinium pyridinium tetrafluoroborate trifluorohydroxyborate (see ref. 10 of R. E. Banks et al., J. Chem. Soc., Chem. Commun. 1992, 595-596).
The present invention provides additional effective electrophilic fluorinating agents which are readily obtainable from starting materials which are presently commercially available in substantial quantities.